Summary

Thrombin Activatable Fibrinolysis Inhibitor (TAFI) is a recentlyidentified fibrinolysis inhibitor in plasma, that when converted to anenzyme potently attenuates fibrinolysis. It is activated by relativelyhigh concentrations of thrombin that exceed the thrombin concentrationrequired for fibrin formation. These high concentrations of thrombinare generated by the intrinsic pathway via activation of factor XI bythrombin. The down regulation of fibrinolysis by TAFI can be meas-uredin a clot lysis assay. When the clot lysis times of healthy individu-alswere determined, large inter-individual differences were observed.To determine if differences in concentration of TAFI explain the varia-tionin clot lysis between individuals, specific assays were developedfor the measurement of TAFI antigen and activity in plasma. In normalplasma, there was a dose-dependent relationship between TAFI antigenand TAFI activity. There was also a correlation between clot lysis timeand plasma TAFI antigen, indicating that the amount of TAFI that is ac-tivatedduring the clot lysis assay, is dependent on the concentration ofTAFI. In the plasmas of 20 healthy individuals, clot lysis times, TAFIantigen and TAFI activity were determined. Both TAFI antigen andTAFI activity showed a significant correlation with the clot lysis time.No correlation between TAFI antigen and clot lysis time was foundwhen the clot lysis time was determined in the presence of an antibodyblocking the factor XI feedback loop. These results indicate that plasmaTAFI levels influence the clot lysis time in healthy individuals in thepresence of an intact intrinsic pathway of coagulation.